Longitudinal measurements of cognition, brain glucose metabolism as determined with positron emission tomography (PET), and brain anatomy using magnetic resonance imaging were conducted in 10 Down syndrome (DS) subjects initially older than 40 years of age. Changes in memory test scores over 7 years preceded the appearance of overt dementia in two subjects, indicating that a pre-dementia prodrome can be identified in subjects with 100% risk of developing Alzheimer's disease (AD). Predementia changes could be identified by submitting the non-demented subjects to audiovisual stimulation while measuring regional glucose metabolism with PET.